Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
1.
BMC Bioinformatics ; 23(1): 328, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941549

RESUMO

BACKGROUND: Single-cell RNA-sequencing is revolutionising the study of cellular and tissue-wide heterogeneity in a large number of biological scenarios, from highly tissue-specific studies of disease to human-wide cell atlases. A central task in single-cell RNA-sequencing analysis design is the calculation of cell type-specific genes in order to study the differential impact of different replicates (e.g. tumour vs. non-tumour environment) on the regulation of those genes and their associated networks. The crucial task is the efficient and reliable calculation of such cell type-specific 'marker' genes. These optimise the ability of the experiment to isolate highly-specific cell phenotypes of interest to the analyser. However, while methods exist that can calculate marker genes from single-cell RNA-sequencing, no such method places emphasise on specific cell phenotypes for downstream study in e.g. differential gene expression or other experimental protocols (spatial transcriptomics protocols for example). Here we present SMaSH, a general computational framework for extracting key marker genes from single-cell RNA-sequencing data which reliably characterise highly-specific and niche populations of cells in numerous different biological data-sets. RESULTS: SMaSH extracts robust and biologically well-motivated marker genes, which characterise a given single-cell RNA-sequencing data-set better than existing computational approaches for general marker gene calculation. We demonstrate the utility of SMaSH through its substantial performance improvement over several existing methods in the field. Furthermore, we evaluate the SMaSH markers on spatial transcriptomics data, demonstrating they identify highly localised compartments of the mouse cortex. CONCLUSION: SMaSH is a new methodology for calculating robust markers genes from large single-cell RNA-sequencing data-sets, and has implications for e.g. effective gene identification for probe design in downstream analyses spatial transcriptomics experiments. SMaSH has been fully-integrated with the ScanPy framework and provides a valuable bioinformatics tool for cell type characterisation and validation in every-growing data-sets spanning over 50 different cell types across hundreds of thousands of cells.


Assuntos
Biologia Computacional , Transcriptoma , Animais , Biomarcadores , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Camundongos , RNA , Análise de Sequência de RNA , Análise de Célula Única/métodos
2.
J Nutr Health Aging ; 21(9): 936-942, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29083433

RESUMO

OBJECTIVES: The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden). DESIGN: All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive). SETTING: Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE. PARTICIPANTS: Mobility-limited (Short Physical Performance Battery (SPPB) ≤9) and vitamin D insufficient (serum 25(OH) D 9 - 24 ng/ml) older adults were recruited for this study. MEASUREMENTS: Primary outcome was gait speed assessed by the 400M walk. RESULTS: 149 subjects were randomized into the study (mean age=77.5±5.4; female=46.3%; mean SPPB= 7.9±1.2; mean 25(OH)D=18.7±6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively. CONCLUSION: Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.


Assuntos
Suplementos Nutricionais/estatística & dados numéricos , Exercício Físico/fisiologia , Avaliação Nutricional , Caminhada/fisiologia , Idoso , Exercício Físico/psicologia , Feminino , Humanos , Masculino
3.
J Nutr Health Aging ; 20(7): 752-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27499309

RESUMO

OBJECTIVES: To describe levels of physical activity among older adults residing at assisted care facilities and their association with physical function. DESIGN: Cross-sectional analysis. SETTING: Assisted care facilities within the greater Boston, MA area. PARTICIPANTS: Older adults aged 65 years and older (N = 65). MEASUREMENTS: Physical Activity Level (PAL) as defined by quartiles from accelerometry (counts and steps), Short Physical Performance Battery (SPPB) Score, gait speed, and handgrip strength. RESULTS: Participants in the most active accelerometry quartile engaged in 25 minutes/week of moderate to vigorous physical activity (MVPA) and walked 2,150 steps/day. These individuals had an SPPB score, 400 meter walk speed, and handgrip strength that was 3.7-3.9 points, 0.3-0.4 meters/second, and 4.5-5.1 kg greater respectively, than individuals in the lowest activity quartile, who engaged in less than 5 min/wk of MVPA or took fewer than 460 steps/day. CONCLUSION: Despite engaging in physical activity levels far below current recommendations (150 min/week of MVPA or > 7000 steps/day), the most active older adults in this study exhibited clinically significant differences in physical function relative to their less active peers. While the direction of causality cannot be determined from this cross-sectional study, these findings suggest a strong association between PAL and physical function among older adults residing in an assisted care facility.


Assuntos
Acelerometria , Exercício Físico/fisiologia , Aptidão Física/fisiologia , Idoso , Idoso de 80 Anos ou mais , Moradias Assistidas , Boston , Estudos Transversais , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Caminhada/fisiologia
4.
Plant Dis ; 98(6): 852, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30708655

RESUMO

Resistant cultivars of hop (Humulus lupulus) have been grown, with the aim of helping to manage powdery mildew in the Pacific Northwest since the first report of the disease in the field in 1997 (4). A major objective of many breeding programs is development of resistance to powdery mildew, and this has generally been achieved by single resistance genes (qualitative resistance). One such gene, R6 (3), has been utilized extensively in new cultivars and has prevented epidemics of the disease in those cultivars across the Pacific Northwestern United States for approximately 15 years. In 2011, a grower in Washington State reported outbreaks of powdery mildew on cv. Apollo, which is thought to possess powdery mildew resistance derived from R6. Fungicides and cultural control measures were applied, and the grower reported no substantial crop damage from the disease. During the winter of 2012, the same grower planted rhizomes of cv. Apollo in a greenhouse in the Yakima Valley of Washington State and later found the plants to be affected by powdery mildew. Affected leaves from plants of cvs. Apollo, Newport, and Nugget (all reported [3] or assumed to possess R6 based on pedigree) grown in the same greenhouse were later provided to the authors. Conidia obtained from each affected plants were transferred to plants of the highly susceptible cv. Symphony, which is not known to contain any resistance genes. After 10 to 14 days of incubation, resultant conidia from each cultivar above (total of three isolates) were transferred to greenhouse grown plants of cvs. Nugget and Symphony and incubated at 18°C. Within 7 days, all three isolates produced powdery mildew colonies characteristic of P. macularis (2) on both cultivars. Cleistothecia did not develop in any colonies. In addition, Nugget and Symphony plants were inoculated with a field population of P. macularis originating from cultivars lacking R6 in Oregon. These inoculations on Nugget did not develop powdery mildew whereas Symphony plants did. Non-inoculated controls remained free of powdery mildew. Results were identical in two additional experiments. The sequence of the mating type idiomorph, MAT1-1, was obtained to confirm identity of the pathogen as P. macularis as described previously (1). The sequences were identical among the three isolates obtained from the greenhouse in Washington and isolates of P. macularis obtained previously from Oregon and Washington. MAT1-2 idiomorph was not detected in the isolates collected. While R6-virulent strains have been detected previously in race characterization experiments, these strains have not caused widespread epidemics of powdery mildew. The increasing prevalence of virulent strains of P. macularis and outbreaks of powdery mildew on formerly resistant cultivars necessitates changes in breeding strategies and disease management efforts to minimize damage resulting from the disease. The distribution of virulent strains of the pathogen and susceptibility of formerly resistance cultivars to powdery mildew are currently under investigation. References: (1) B. Asalfet et al. Phytopathology 103:717, 2013. (2) R. Bélanger et al. The Powdery Mildews: a Comprehensive Treatise. APS Press, St. Paul, MN, 2002. (3) P. Darby. Brew Hist. 121:94, 2005. (4) C. Ocamb et al. Plant Dis. 83:1072, 1999.

5.
Surg Endosc ; 21(1): 53-6, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17031745

RESUMO

BACKGROUND: The introduction of the RP6 (InTouch Health, Santa Barbara, CA, USA) remote-presence "robot" appears to offer a useful telemedicine device. The authors describe the deployment and early experience with the RP6 in a community hospital and provided a live demonstration of the system on April 16, 2005 during the Emerging Technologies Session of the 2005 SAGES Meeting in Fort Lauderdale, Florida. METHODS: The RP6 is a 5-ft 4-in. tall, 215-pound robot that can be remotely controlled from an appropriately configured computer located anywhere on the Internet (i.e., on this planet). The system is composed of a control station (a computer at the central station), a mechanical robot, a wireless network (at the remote facility: the hospital), and a high-speed Internet connection at both the remote (hospital) and central locations. The robot itself houses a rechargeable power supply. Its hardware and software allows communication over the Internet with the central station, interpretation of commands from the central station, and conversion of the commands into mechanical and nonmechanical actions at the remote location, which are communicated back to the central station over the Internet. The RP6 system allows the central party (e.g., physician) to control the movements of the robot itself, see and hear at the remote location (hospital), and be seen and heard at the remote location (hospital) while not physically there. RESULTS: Deployment of the RP6 system at the hospital was accomplished in less than a day. The wireless network at the institution was already in place. The control station setup time ranged from 1 to 4 h and was dependent primarily on the quality of the Internet connection (bandwidth) at the remote locations. Patients who visited with the RP6 on their discharge day could be discharged more than 4 h earlier than with conventional visits, thereby freeing up hospital beds on a busy med-surg floor. Patient visits during "off hours" (nights and weekends) were three times more efficient than conventional visits during these times (20 min per visit vs 40-min round trip travel + 20-min visit). Patients and nursing personnel both expressed tremendous satisfaction with the remote-presence interaction. CONCLUSIONS: The authors' early experience suggests a significant benefit to patients, hospitals, and physicians with the use of RP6. The implications for future development are enormous.


Assuntos
Hospitais Comunitários , Assistência ao Paciente/instrumentação , Robótica , Telemedicina/instrumentação , Atitude , Desenho de Equipamento , Humanos , Enfermeiras e Enfermeiros/psicologia , Alta do Paciente , Satisfação do Paciente , Fatores de Tempo
6.
Radiat Prot Dosimetry ; 120(1-4): 421-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16785245

RESUMO

MIDN (MIcroDosimetry iNstrument) is a payload on the MidSTAR-I spacecraft (Midshipman Space Technology Applications Research) under development at the United States Naval Academy. MIDN is a solid-state system being designed and constructed to measure microdosimetric spectra to determine radiation quality factors for space environments. Radiation is a critical threat to the health of astronauts and to the success of missions in low-Earth orbit and space exploration. The system will consist of three separate sensors, one external to the spacecraft, one internal and one embedded in polyethylene. Design goals are mass <3 kg and power <2 W. The MidSTAR-I mission in 2006 will provide an opportunity to evaluate a preliminary version of this system. Its low power and mass makes it useful for the International Space Station and manned and unmanned interplanetary missions as a real-time system to assess and alert astronauts to enhanced radiation environments.


Assuntos
Radiação Cósmica , Exposição Ocupacional/análise , Proteção Radiológica/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Voo Espacial/instrumentação , Dosimetria Termoluminescente/instrumentação , Relação Dose-Resposta à Radiação , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização , Doses de Radiação , Reprodutibilidade dos Testes , Pesquisa , Sensibilidade e Especificidade , Voo Espacial/métodos , Propriedades de Superfície , Dosimetria Termoluminescente/métodos , Interface Usuário-Computador
7.
Artigo em Inglês | MEDLINE | ID: mdl-16645885

RESUMO

A defining feature of active sensing is the use of self-generated energy to probe the environment. Familiar biological examples include echolocation in bats and dolphins and active electrolocation in weakly electric fish. Organisms that utilize active sensing systems can potentially exert control over the characteristics of the probe energy, such as its intensity, direction, timing, and spectral characteristics. This is in contrast to passive sensing systems, which rely on extrinsic energy sources that are not directly controllable by the organism. The ability to control the probe energy adds a new dimension to the task of acquiring relevant information about the environment. Physical and ecological constraints confronted by active sensing systems include issues of signal propagation, attenuation, speed, energetics, and conspicuousness. These constraints influence the type of energy that organisms use to probe the environment, the amount of energy devoted to the process, and the way in which the nervous system integrates sensory and motor functions for optimizing sensory acquisition performance.


Assuntos
Comportamento Animal/fisiologia , Sensação/fisiologia , Órgãos dos Sentidos/fisiologia , Animais , Ecolocação/fisiologia , Transferência de Energia
8.
J Exp Biol ; 208(Pt 15): 2981-3001, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16043603

RESUMO

Nicotinic transmission in the enteric nervous system (ENS) is extensive, but the role of individual nicotinic acetylcholine receptor (nAChR) subtypes in the functional connectivity of its plexuses has been elusive. Using monoclonal antibodies (mAbs) against neuronal alpha3-, alpha4-, alpha3/alpha5-, beta2-, beta4- and alpha7-subunits, combined with radioimmunoassays and immunocytochemistry, we demonstrate that guinea-pig enteric ganglia contain all of these nAChR-subunits with the exception of alpha4, and so, differ from mammalian brain. This information alone, however, is insufficient to establish the functional role of the identified nAChR-subtypes within the enteric networks and, ultimately, their specific contributions to gastrointestinal physiology. We have used voltage-sensitive dyes and a high-speed CCD camera, in conjunction with specific antagonists to various nAChRs, to elucidate some of the distinct contributions of the individual subtypes to the behaviour of enteric networks. In the guinea-pig, the submucous plexus has the extraordinary advantage that it is virtually two-dimensional, permitting optical recording, with single cell resolution, of the electrical activity of all of its neurones. In this plexus, the block of alpha3beta2-, alpha3beta4- and/or alpha7-nAChRs always results in a decrease in the magnitude of the synaptic response. However, the magnitude of the fast excitatory post-synaptic potentials (epsps) evoked by electrical stimulation of a neighbouring ganglion varies from cell to cell, reflecting the differential expression of subunits already observed using mAbs, as well as the strengths of the activated synaptic inputs. At the same time, we observe that submucous neurones have a substantial mecamylamine (Mec)-insensitive (non-nicotinic) component to their fast epsps, which may point to the presence of purinergic or serotonergic fast epsps in this system. In the myenteric plexus, on the other hand, the antagonist-induced changes in the evoked synaptic response vary depending upon the location of the stimulating electrode with respect to the ganglion under study. The range of activity patterns that follows sequential pharmacological elimination of individual subtypes suggests that nAChRs may be capable of regulating the activity of both excitatory and inhibitory pathways, in a manner similar to that described in the central nervous system.


Assuntos
Sistema Nervoso Entérico/metabolismo , Cobaias/metabolismo , Subunidades Proteicas/metabolismo , Receptores Nicotínicos/metabolismo , Transmissão Sináptica/fisiologia , Animais , Anticorpos Monoclonais , Encéfalo/metabolismo , Sistema Nervoso Entérico/fisiologia , Potenciais Evocados/fisiologia , Imuno-Histoquímica , Intestino Delgado/metabolismo , Radioimunoensaio , Gravação em Vídeo
10.
J Parasitol ; 90(6): 1361-5, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15715229

RESUMO

To determine whether deer can transmit Neospora caninum, brains of naturally infected white-tailed deer (Odocoileus virginianus) were fed to 4 dogs; 2 of these dogs shed oocysts. Oocysts from 1 of the dogs were tested by polymerase chain reaction and found to be positive for N. caninum and negative for Hammondia heydorni. The internal transcribed spacer 1 sequence of the new strain (designated NC-deer1) was identical to N. caninum from domestic animals, indicating that N. caninum is transmitted between wild and domestic animals, often enough to prevent divergent evolution of isolated populations of the parasite. NC-deerl oocysts were administered to a calf that developed a high antibody titer, providing evidence that N. caninum from wildlife can infect cattle. In addition, N. caninum antibody seroprevalence was detected in 64/164 (39%) free-ranging gray wolves (Canis lupus), 12/113 (11%) coyotes (Canis latrans), 50/193 (26%) white-tailed deer, and 8/61 (13%) moose (Alces alces). These data are consistent with a sylvatic transmission cycle of N. caninum between cervids and canids. We speculate that hunting by humans favors the transmission of N. caninum from deer to canids, because deer carcasses are usually eviscerated in the field. Infection of canids in turn increases the risk of transmitting the parasite to domestic livestock.


Assuntos
Coccidiose/veterinária , Cervos/parasitologia , Doenças do Cão/transmissão , Neospora/patogenicidade , Animais , Animais Domésticos , Animais Selvagens , Anticorpos Antiprotozoários/sangue , Bovinos , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/transmissão , Coccidiose/epidemiologia , Coccidiose/transmissão , Coiotes , Reações Cruzadas , DNA de Protozoário/análise , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Fezes/parasitologia , Feminino , Illinois/epidemiologia , Masculino , Neospora/genética , Neospora/imunologia , Reação em Cadeia da Polimerase , Sarcocystidae/genética , Sarcocystidae/imunologia , Sarcocystidae/isolamento & purificação , Estudos Soroepidemiológicos , Toxoplasma/imunologia , Lobos
11.
Cell Transplant ; 12(3): 291-303, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12797383

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for noradrenergic (NE) neurons of the pontine nucleus locus coeruleus (LC). Decreased function of the LC-NE neurons has been found during normal aging and in neurodegenerative disorders. We have previously shown that GDNF participates in the differentiation of LC-NE neurons during development. However, the continued role of GDNF for LC-NE neurons during maturation and aging has not been addressed. We examined alterations in aged mice that were heterozygous for the GDNF gene (Gdnf+/-). Wild-type (Gdnf+/+) and Gdnf+/- mice (18 months old) were tested for locomotor activity and brain tissues were collected for measuring norepinephrine levels and uptake, as well as for morphological analysis. Spontaneous locomotion was reduced in Gdnf+/- mice in comparison with Gdnf+/+ mice. The reduced locomotor activity of Gdnf+/- mice was accompanied by reductions in NE transporter activity in the cerebellum and brain stem as well as decreased norepinephrine tissue levels in the LC. Tyrosine hydroxylase (TH) immunostaining demonstrated morphological alterations of LC-NE cell bodies and abnormal TH-positive fibers in the hippocampus, cerebellum, and frontal cortex of Gdnf+/- mice. These findings suggest that the LC-NE system of Gdnf+/- mice is impaired and suggest that GDNF plays an important role in continued maintenance of this neuronal system throughout life.


Assuntos
Envelhecimento/fisiologia , Locus Cerúleo/metabolismo , Fatores de Crescimento Neural/metabolismo , Norepinefrina/metabolismo , Animais , Química Encefálica , Tronco Encefálico/metabolismo , Cerebelo/citologia , Cerebelo/metabolismo , Lobo Frontal/citologia , Lobo Frontal/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Hipocampo/citologia , Hipocampo/metabolismo , Locus Cerúleo/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/fisiologia , Fatores de Crescimento Neural/genética , Neurônios/fisiologia , Norepinefrina/química , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Simportadores/metabolismo , Sinaptossomos/química , Sinaptossomos/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
13.
Cell Transplant ; 12(3): 291-303, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28853928

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for noradrenergic (NE) neurons of the pontine nucleus locus coeruleus (LC). Decreased function of the LC-NE neurons has been found during normal aging and in neurodegenerative disorders. We have previously shown that GDNF participates in the differentiation of LC-NE neurons during development. However, the continued role of GDNF for LC-NE neurons during maturation and aging has not been addressed. We examined alterations in aged mice that were heterozygous for the GDNF gene (Gdnf+/-). Wild-type (Gdnf+/+) and Gdnf+/- mice (18 months old) were tested for locomotor activity and brain tissues were collected for measuring norepinephrine levels and uptake, as well as for morphological analysis. Spontaneous locomotion was reduced in Gdnf+/- mice in comparison with Gdnf+/+ mice. The reduced locomotor activity of Gdnf +/- mice was accompanied by reductions in NE transporter activity in the cerebellum and brain stem as well as decreased norepinephrine tissue levels in the LC. Tyrosine hydroxylase (TH) immunostaining demonstrated morphological alterations of LC-NE cell bodies and abnormal TH-positive fibers in the hippocampus, cerebellum, and frontal cortex of Gdnf+/- mice. These findings suggest that the LC-NE system of Gdnf+/- mice is impaired and suggest that GDNF plays an important role in continued maintenance of this neuronal system throughout life.

14.
Radiat Prot Dosimetry ; 101(1-4): 129-32, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12382721

RESUMO

The feasibility was investigated of a solid-state neutron detector/dosemeter based on single-event upset (SEU) effects in dynamic random-access memories (DRAMs), commonly used in computer memories. Such a device, which uses a neutron converter material to produce a charged particle capable of causing an upset, would be light-weight, low-power, and could be read simply by polling the memory for bit flips. It would have significant advantages over standard solid-state neutron dosemeters which require off-line processing for track etching and analysis. Previous efforts at developing an SEU neutron detector/dosemeter have suffered from poor response, which can be greatly enhanced by selecting a modern high-density DRAM chip for SEU sensitivity and by using a thin 10B film as a converter. Past attempts to use 10B were not successful because the average alpha particle energy was insufficient to penetrate to the sensitive region of the memory. This can be overcome by removing the surface passivation layer before depositing the 10B film or by implanting 10B directly into the chip. Previous experimental data show a 10(3) increase in neutron sensitivity by chips containing borosilicate glass, which could be used in an SEU detector. The results are presented of simulations showing that the absolute efficiency of an SEU neutron dosemeter can be increased by at least a factor of 1000 over earlier designs.


Assuntos
Nêutrons , Radiometria/métodos , Dispositivos de Armazenamento em Computador , Estudos de Viabilidade , Radiometria/instrumentação , Sensibilidade e Especificidade
15.
J Gen Physiol ; 118(5): 563-82, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11696612

RESUMO

We characterized the functional and molecular properties of nicotinic acetylcholine receptors (AChRs) expressed by IMR-32, a human neuroblastoma cell line, and compared them to human alpha3 AChRs expressed in stably transfected human embryonic kidney (HEK) cells. IMR-32 cells, like neurons of autonomic ganglia, have been shown to express alpha3, alpha5, alpha7, beta2, and beta4 AChR subunits. From these subunits, several types of alpha3 AChRs as well as homomeric alpha7 AChRs could be formed. However, as we show, the properties of functional AChRs in these cells overwhelmingly reflect alpha3beta4 AChRs. alpha7 AChR function was not detected, yet we estimate that there are 70% as many surface alpha7 AChRs in IMR-32 when compared with alpha3 AChRs. Agonist potencies (EC(50) values) followed the rank order of 1,1-dimethyl-4-phenylpiperazinium (DMPP; 16+/-1 microM) > nicotine (Nic; 48 +/- 7 microM) > or = cytisine (Cyt; 57 +/- 3 microM) = acetylcholine (ACh; 59 +/- 6 microM). All agonists exhibited efficacies of at least 80% relative to ACh. The currents showed strong inward rectification and desensitized at a rate of 3 s(-1) (300 microM ACh; -60 mV). Assays that used mAbs confirmed the predominance of alpha3- and beta4-containing AChRs in IMR-32 cells. Although 18% of total alpha3 AChRs contained beta2 subunits, no beta2 subunit was detected on the cell surface. Chronic Nic incubation increased the amount of total, but not surface alpha3beta2 AChRs in IMR-32 cells. Nic incubation and reduced culture temperature increased total and surface AChRs in alpha3beta2 transfected HEK cells. Characterization of various alpha3 AChRs expressed in HEK cell lines revealed that the functional properties of the alpha3beta4 cell line best matched those found for IMR-32 cells. The rank order of agonist potencies (EC(50) values) for this line was DMPP (14 +/- 1 microM) = Cyt (18 +/- 1 microM) > Nic (56 +/- 15 microM > ACh (79 +/- 8 microM). The efficacies of both Cyt and DMPP were approximately 80% when compared with ACh and the desensitization rate was 2 s(-1). These data show that even with the potential to express several human nicotinic AChR subtypes, the functional properties of AChRs expressed by IMR-32 are completely attributable to alpha3beta4 AChRs.


Assuntos
Acetilcolina/farmacologia , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/fisiologia , Alcaloides/farmacologia , Azocinas , Linhagem Celular , Iodeto de Dimetilfenilpiperazina/farmacologia , Humanos , Rim/citologia , Neuroblastoma/patologia , Nicotina/farmacologia , Técnicas de Patch-Clamp , Quinolizinas , Temperatura , Transfecção , Células Tumorais Cultivadas/fisiologia
17.
J Rheumatol ; 28(7): 1655-65, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11469475

RESUMO

OBJECTIVE: To test the effects of a high intensity home-based progressive strength training program on the clinical signs and symptoms of osteoarthritis (OA) of the knee. METHODS: Forty-six community dwelling patients, aged 55 years or older with knee pain and radiographic evidence of knee OA, were randomized to a 4 month home based progressive strength training program or a nutrition education program (attention control). Thirty-eight patients completed the trial with an adherence of 84% to the intervention and 65% to the attention control. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index pain and physical function subscales. Secondary outcomes included clinical knee examination, muscle strength, physical performance measures, and questionnaires to measure quality of life variables. RESULTS: Patients in the strength training group who completed the trial had a 71% improvement in knee extension strength in the leg reported as most painful versus a 3% improvement in the control group (p < 0.01). In a modified intent to treat analysis, self-reported pain improved by 36% and physical function by 38% in the strength training group versus 11 and 21%, respectively, in the control group (p = 0.01 for between group comparison). In addition, those patients in the strength training group who completed the trial had a 43% mean reduction in pain (p = 0.01 vs controls), a 44% mean improvement in self-reported physical function (p < 0.01 vs controls), and improvements in physical performance, quality of life, and self-efficacy when compared to the control group. CONCLUSION: High intensity, home based strength training can produce substantial improvements in strength, pain, physical function and quality of life in patients with knee OA.


Assuntos
Terapia por Exercício , Osteoartrite do Joelho/terapia , Idoso , Feminino , Serviços de Assistência Domiciliar , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Osteoartrite do Joelho/psicologia , Medição da Dor , Qualidade de Vida , Recuperação de Função Fisiológica
18.
J Appl Physiol (1985) ; 90(6): 2117-29, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11356774

RESUMO

Increased gait instability is common in older adults, even in the absence of overt disease. The goal of the present study was to quantitatively investigate the factors that contribute to gait instability and its potential reversibility in functionally impaired older adults. We studied 67 older men and women with functional impairment before and after they participated in a randomized placebo-controlled, 6-mo multimodal exercise trial. We found that 1) gait instability is multifactorial; 2) stride time variability is strongly associated with functional status and performance-based measures of function that have previously been shown to predict significant clinical outcomes such as morbidity and nursing home admission; 3) neuropsychological status and health-related quality of life play important, independent roles in gait instability; and 4) improvement in physiological capacity is associated with reduced gait instability. Although the etiology of gait instability in older persons with mild-moderate functional impairment is multifactorial, interventions designed to reduce gait instability may be effective in bringing about a more consistent and more stable walking pattern.


Assuntos
Exercício Físico/fisiologia , Marcha/fisiologia , Aptidão Física/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Equilíbrio Postural/fisiologia , Qualidade de Vida
19.
J Exp Biol ; 204(Pt 3): 543-57, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11171305

RESUMO

Animals can actively influence the content and quality of sensory information they acquire from the environment through the positioning of peripheral sensory surfaces. This study investigated receptor surface positioning during prey-capture behavior in weakly electric gymnotiform fish of the genus Apteronotus. Infrared video techniques and three-dimensional model-based tracking methods were used to provide quantitative information on body position and conformation as black ghost (A. albifrons) and brown ghost (A. leptorhynchus) knifefish hunted for prey (Daphnia magna) in the dark. We found that detection distance depends on the electrical conductivity of the surrounding water. Best performance was observed at low water conductivity (2.8 cm mean detection distance and 2 % miss rate at 35 microS cm(-)(1), A. albifrons) and poorest performance at high conductivity (1.5 cm mean detection distance and 11 % miss rate at 600 microS cm(-)(1), A. albifrons). The observed conductivity-dependence implies that nonvisual prey detection in Apteronotus is likely to be dominated by the electrosense over the range of water conductivities experienced by the animal in its natural environment. This result provides the first evidence for the involvement of electrosensory cues in the prey-capture behavior of gymnotids, but it leaves open the possibility that both the high-frequency (tuberous) and low-frequency (ampullary) electroreceptors may contribute. We describe an electrosensory orienting response to prey, whereby the fish rolls its body following detection to bring the prey above the dorsum. This orienting response and the spatial distribution of prey at the time of detection highlight the importance of the dorsal surface of the trunk for electrosensory signal acquisition. Finally, quantitative analysis of fish motion demonstrates that Apteronotus can adapt its trajectory to account for post-detection motion of the prey, suggesting that it uses a closed-loop adaptive tracking strategy, rather than an open-loop ballistic strike strategy, to intercept the prey.


Assuntos
Comportamento Animal/fisiologia , Animais , Locomoção/fisiologia , Células Receptoras Sensoriais/fisiologia , Eletricidade Estática
20.
J Gerontol A Biol Sci Med Sci ; 55(12): M757-60, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11129399

RESUMO

BACKGROUND: Declining resting energy expenditure (REE) is a hallmark of normal aging, but the cause of this decline remains controversial. Some, but not all, studies have shown that the decline in REE with age is eliminated after adjustment for fat-free mass (FFM). METHODS: We examined the effect of four body composition methods used to assess FFM (underwater weighing [UWW], bioimpedance analysis [BIA], tritium dilution, and total body potassium [TBK]) on the relationship between REE and age in 30 healthy men and 101 healthy women aged 18 to 87 years. RESULTS: The decline in REE with age was significant in women (-80.3 kJ/d/y, p < .004) but not in men (-46.9 kJ/d/y, p = .328). After adjustment for FFM, the decline in REE with age persisted when FFM was measured by BIA, UWW, or tritium dilution, but no decline was seen when TBK was used to adjust for FFM. In both women and men, fat mass was significantly associated with REE after adjusting for age and FFM. CONCLUSION: It is the decline in cell mass with age, detectable by TBK but not by other methods, rather than any metabolic alteration, that explains the decline in FFM-adjusted REE with age.


Assuntos
Envelhecimento/metabolismo , Composição Corporal , Caracteres Sexuais , Magreza , Adulto , Idoso , Impedância Elétrica , Metabolismo Energético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descanso
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...